The broad immunopathologic spectrum of leprosy ranging from strong manifestations of cellular immunity at the tuberculoid pole and humoral antibody manifestations at the lepromatous pole provides a single pathogen/single host model for the study of macrophage deficiency at the lepromatous pole. Eluciation of these functional and possible enzymatic deficiencies in contrast to the effectiveness of cellular immunity at the tuberculoid pole provides a model for enhanced understanding of the relationships between cellular immunity and cell enzymology. To this end lipid, polysaccharide and wax components of M. leprae are used to challenge human macrophages in tissue culture and in vivo by the Rebuck window technic. The enzymatic and intracellular responses are evaluated by means of electron microscopy and histochemistry, comparing the lepromatous and tuberculoid macrophage response. By these technics a possible and dramatic defect in lepromatous cells is sought as an explanation for the inability of these cells to effectively dispose of M. leprae and its degenerative product.